Synthesis
General procedure for the synthesis of 5-fluoro-2-aminothiazoles from N-(5-fluoro-2-thiazolyl)-carbamic acid-1,1-dimethylethyl ester: trifluoroacetic acid (TFA, 27.43 g, 241.00 mmol) was added to tert-butyl N-(5-fluoro-2-thiazolyl)carbamate (10.50 g, 48.1 mmol) in dichloromethane (CH2Cl2, a 100 mL) solution. The reaction mixture was stirred for 3 h at room temperature and then the solvent was removed by rotary evaporator under reduced pressure. The residue was neutralized with aqueous sodium bicarbonate (NaHCO3) and subsequently extracted with dichloromethane (20 mL × 3). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate and filtered, and concentrated under reduced pressure to give 5-fluoro-2-aminothiazole as a gray solid in a yield of 5.2 g (91.5% yield). Nuclear magnetic resonance hydrogen spectrum (1H NMR, 400 MHz, CDCl3) δ 6.65 (d, J = 2.6 Hz, 1H), 4.69 (br s, 2H). Electrospray ionization mass spectrometry (ESI-MS) m/z calculated value [C3H3FN2S]+ [M + H]+: 119.0; measured value: 119.0.
References
[1] Patent: WO2018/11093, 2018, A1. Location in patent: Page/Page column 112
[2] Patent: US2007/213349, 2007, A1. Location in patent: Page/Page column 67
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 11, p. 3875 - 3884
